We have previously shown that C3b resides in a protected site when it is covalently bound to IgG (C3b-IgG). Such C3b displays a reduced affinity for factor H, with consequent enhanced survival in the presence of factors H and I. Since erythrocyte CR1 may be a major co-factor for factor I-mediated inactivation of immune complex-borne C3b in blood, we have examined the effect of covalently bound IgG on the C3b-CR1 interaction. Binding of monomeric C3b and C3b-IgG to human erythrocyte CR1 demonstrates identical ionic strength dependence for both species. Identical numbers of binding sites with indistinguishable affinities are detected by both ligands. Cleavage of the 'chain of C3b and the'-heavy chain of C3b-IgG proceeds at the same rate when CR1 serves as co-factor for factor I. CR1 supports a second cleavage of fluid phase iC3b1 chain that generates C3c and a 33,000 m.w. fragment, which bears antigenic markers characteristic of C3g. Inactivation of C3b and C3b-IgG by CR1 and factor I can occur at physiologic ionic strength, but proceeds slowly relative to rates attainable with sub-physiologic inputs of factor H. Thus, inactivation of C3b-IgG hetero-dimers or small immune complexes bearing limited numbers of C3b residues may remain largely factor H-dependent in vivo, with resultant enhanced C3b survival. Since coating of bacteria with specific IgG antibodies enhances complement-mediated bacterial killing and simultaneously provides the opportunity for the formation of C3b-IgG, we additionally studied the role of C3b-IgG in complement-mediated bacterial lysis. Bacteria were coated with C3b alone, C3b followed by specific IgG, or preformed covalent hetero-dimers of C3b and specific IgG. The latter species demonstrated a 4 to 10 fold enhancement of its capacity to support alternative-pathway bacterial killing. This effect was not dependent on aggregation or total levels of C3b uptake--and may represent a new and important role for IgG in enhancing serum-mediated killing of gram-negative bacillary pathogens.